Mechanisms of coronary hyperconstriction in response to serotonin induced by X-irradiation in miniature pigs: increased constrictive response of medial smooth muscle.

Experimental and clinical studies suggest that X-irradiation to the coronary artery may enhance vasoconstrictive response. This study aimed to clarify the effect of X-irradiation on the vasomotor response of porcine coronary artery. X-ray (15 Gy) was selectively irradiated to the left anterior descending coronary artery (LAD) in 14 Gottingen miniature pigs. The coronary vasomotor responses to serotonin at the irradiated site (LAD) and the control site (the left circumflex artery; LCX) were assessed by quantitative arteriography before and 1 h and 1, 2, and 4 weeks after X-irradiation. At 2 weeks, endothelium-dependent vasodilation in response to substance P was also evaluated arteriographically in vivo. At 2 weeks, isometric tension studies were performed to evaluate the constrictive responses of medial muscle strips and endothelium-dependent relaxation. Coronary vasoconstriction in response to serotonin was enhanced 1 week after, and further augmentation was noted 2 and 4 weeks after X-irradiation. Endothelium-dependent vasodilation in response to substance P in vivo was preserved 2 weeks after X-irradiation. Coronary arteriography showed no organic stenosis at the irradiated site. In vitro studies demonstrated that medial muscle strips of the irradiated site showed hypercontraction in response to serotonin and that endothelium-dependent relaxation in response to serotonin and substance P was preserved at the irradiated site. A histological study revealed no appreciable changes of the endothelial cells or intimal thickening. These results suggest that coronary vasoconstriction in response to serotonin was enhanced 1 week after X-irradiation, and that this hyperconstriction was caused by the increased constrictive response of medial smooth muscle, but not by impaired endothelium-dependent relaxation or by a geometric effect due to intimal thickening.